Gap junctions can now be characterized in terms of at least five parameters: conductance, permeability, pH dependence, divalent ion dependence, and voltage dependence. We are analyzing these properties in terms of interactions between treatments and effects of other treatments such as octanol, aldehyde fixatives and group-specific protein reagents. Physiological studies are correlated with fine structural investigations involving freeze fracture and thin sectioning. The goals are to evaluate single channel conductance and permeability and physiological factors controlling conductance. We hope to implicate specific amino acid residues as involved in gating and integrity of junctional membranes.